RESUMO
The single zeta globin gene rearrangement (-zeta/) is an unusual mutation associated with the alpha globin gene cluster on chromosome 16p13.3. It has been detected regularly among West Africans (gene frequency approximately 0.05) and sporadically among other populations. DNA samples from 186 Polynesian Niueans living in Auckland, New Zealand, were studied. Eighteen (gene frequency 0.05) were shown to have the -zeta/gene arrangement, which results from loss of the psi zeta 1 gene. Hematological phenotypes in six cord blood samples and 12 affected adults were normal. The high frequency for -zeta/in Niueans may represent another example of genetic drift and a founder effect in Polynesians or may reflect a different founding population.
Assuntos
Globinas/genética , Cromossomos Humanos Par 16 , Frequência do Gene , Rearranjo Gênico , Genes , Humanos , Nova Zelândia , Polinésia/etnologiaRESUMO
Prenatal diagnoses of the genetic disorders alpha, beta thalassemia, HbS, Hb Lepore, hemophilia and cystic fibrosis were sought in 88 cases. Six unsuccessful attempts at diagnosis resulted from DNA polymorphisms which were only 50% informative (four cases) and prenatal diagnoses which had been undertaken before it was known whether DNA polymorphisms in family studies were informative (two cases). The most frequent indications for prenatal diagnosis were the hemoglobinopathies although requests for exclusion of cystic fibrosis formed the majority during 1989. Strong linkage disequilibrium between the cystic fibrosis defect and its associated DNA polymorphisms facilitated detection of this disorder. Late presentations among patients with beta thalassemia and hemophilia and the necessity for more specialised genetic counselling were the commonest problems encountered.
Assuntos
Mapeamento Cromossômico , Doenças Genéticas Inatas/diagnóstico , Biologia Molecular/métodos , Diagnóstico Pré-Natal/métodos , Fibrose Cística/diagnóstico , Fibrose Cística/genética , Doenças Fetais/diagnóstico , Doenças Fetais/genética , Doenças Genéticas Inatas/genética , Ligação Genética/genética , Hemoglobinopatias/diagnóstico , Hemoglobinopatias/genética , Hemofilia A/diagnóstico , Hemofilia A/genética , Humanos , Linhagem , Polimorfismo Genético/genéticaRESUMO
Alpha zero-thalassaemia of the British type is described for the first time in a New Zealand family. Microcytic, hypochromic red blood cells were found in affected individuals. Exclusion of iron deficiency and beta-thalassaemia suggested alpha-thalassaemia as a possible cause. This was confirmed by the detection of haemoglobin (Hb) H inclusion bodies. Definitive characterisation of the alpha-thalassaemia defect required DNA mapping which demonstrated the British alpha zero-thalassaemia deletion involving both alpha globin genes. alpha zero-thalassaemia should no longer be considered a disorder affecting individuals of Mediterranean or Asian backgrounds. Anglo-Saxons are also an at risk group. Co-inheritance of this abnormality with a second alpha-thalassaemia defect can lead to Hb H disease or Hb Bart's hydrops fetalis.
Assuntos
Talassemia/genética , Adolescente , Adulto , Criança , Mapeamento Cromossômico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Linhagem , Talassemia/sangue , Talassemia/epidemiologia , Reino UnidoRESUMO
The clinical spectrum of HbH disease varies from a benign disorder to a severe anemia which is blood-transfusion dependent. Heterogeneity at the clinical level is now being understood in terms of the underlying molecular defects. In this study a mild phenotype found in a group of patients with HbH disease is associated with two types of alpha-thalassemia. These are: alpha+-thalassemia (-alpha 3.7/) and alpha 0-thalassemia (--SEA/). In contrast, a second group with more severe HbH disease has a non-deletional alpha-thalassemia defect instead of alpha+-thalassemia (genotype alpha alpha T/--SEA). In the majority of cases, the basis for non-deletional alpha-thalassemia is Hb Constant Spring.
Assuntos
Marcadores Genéticos/sangue , Hemoglobina H/genética , Hemoglobinas Anormais/genética , Talassemia/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Talassemia/classificação , Talassemia/etnologiaRESUMO
Globin gene mapping data enable Polynesians to be divided into three distinct groups: (i) Maoris, Cook Islanders, (ii) Tongans, Samoans, (iii) Niue Islanders. Unusual RFLPs detected by the restriction enzymes Apa I and Bgl II are found in Polynesians. A high frequency of alpha-thalassemia in this population is explained by genetic drift and a founder effect.
Assuntos
Globinas/genética , Frequência do Gene , Rearranjo Gênico , Humanos , Programas de Rastreamento , Polimorfismo de Fragmento de Restrição , PolinésiaRESUMO
Rearrangements involving genes of the alpha- and beta-globin loci were frequently detected in DNA from Polynesians. A founder effect and genetic drift occurring 2,000-3,000 years ago as Polynesians migrated eastward across the Pacific is proposed as the likely mechanism for these genetic changes that include deletions or additions of alpha-, gamma-, and zeta-globin genes and an unusual restriction fragment length polymorphism (RFLP) associated with the zeta gene. Preliminary data show different frequencies for gene rearrangements between island groups. Further study of these differences should provide additional information on the prehistory of Polynesians.
Assuntos
Genética Populacional , Globinas/genética , Mapeamento Cromossômico , Humanos , Linhagem , Polinésia , Talassemia/genéticaRESUMO
Alpha thalassemia is rarely diagnosed in Australian families of British or Northern European ancestry. In 1972, a third generation Australian was shown to have alpha thalassemia. In the absence of known Mediterranean or South East Asian ancestry it was reported as being the first example of alpha thalassemia in an Australian family. Further study of the proposita in 1985 using DNA mapping of the alpha globin gene complex, shows a distinctive molecular defect identical to the British type of alpha thalassemia. The latter is clearly different from the commonly encountered Mediterranean and South East Asian alpha zero haplotypes. Recognition that alpha zero thalassemia occurs in Australians is important since it may produce a microcytic hypochromic anemia. Its inheritance together with other forms of alpha thalassemia may lead to severe Hb H disease or Hb Bart's hydrops fetalis.
Assuntos
Talassemia/genética , Adulto , Austrália , DNA/genética , DNA/isolamento & purificação , Enzimas de Restrição do DNA , Feminino , Triagem de Portadores Genéticos , Homozigoto , Humanos , Masculino , Talassemia/sangue , Reino Unido/etnologiaRESUMO
Severe Hb H disease presented in unexpected ways in 2 families of Greek origin. In 1, Hb H disease led to neonatal death. The underlying molecular defect was double-heterozygosity for the --Med/ alpha thalassaemia haplotype and a nondeletional alpha thalassaemia defect (alpha alpha T'Karditsa'/). The 2nd family requested antenatal diagnosis. The husband had mild nondeletional alpha thalassaemia. Initial investigations in the wife demonstrated unexpected gene mapping patterns. These have recently been shown to result from the (-alpha)Med 20.5/ haplotype.
Assuntos
Hemoglobina H/genética , Hemoglobinas Anormais/genética , Talassemia/genética , Mapeamento Cromossômico , DNA/genética , Enzimas de Restrição do DNA , Humanos , Linhagem , Talassemia/fisiopatologiaRESUMO
Function of the triplicated alpha alpha alpha 4.2/gene rearrangement was assessed by measurement of Hb Bart's and hematological phenotype including alpha/beta biosynthesis ratio. Increased output of alpha globin chains in alpha alpha alpha 4.2/-- compared to alpha alpha/-- was found in a cord blood. In contrast, hematological phenotypes in two family members with the alpha alpha alpha 4.2/-- genotype were consistent with that expected in alpha alpha/--. This would suggest that the additional alpha gene in the alpha alpha alpha 4.2/rearrangement has variable expression.
Assuntos
Mapeamento Cromossômico , Hemoglobinas Anormais/fisiologia , DNA/análise , Eletroforese em Acetato de Celulose , Feminino , Sangue Fetal/análise , Genótipo , Hemoglobinas Anormais/genética , Humanos , Recém-Nascido , Masculino , Talassemia/sangueRESUMO
DNA mapping of the alpha globin gene cluster in cord blood from Polynesians has shown an increased frequency of alpha thalassaemia and triplicated alpha genes. Reduced levels of haemoglobin, mean corpuscular haemoglobin or mean corpuscular volume in these neonates may indicate alpha thalassaemia. Recognition of this will avoid unnecessary haematological investigations and iron supplementation.
Assuntos
Índices de Eritrócitos , Hemoglobinas/análise , Talassemia/sangue , Mapeamento Cromossômico , DNA/genética , Sangue Fetal/análise , Genótipo , Hemoglobinas Anormais/análise , Humanos , Recém-Nascido , Nova Zelândia , Linhagem , Polinésia/etnologia , Talassemia/genéticaRESUMO
Using gene mapping, 16.3% of Polynesians were shown to have alpha thalassemia. These results are surprising since malaria is not found in Polynesia. Moreover, triplicated alpha gene rearrangements were identified in a further 7.7%, a frequency not seen in other populations.
Assuntos
Mapeamento Cromossômico , Globinas/genética , Malária/genética , Enzimas de Restrição do DNA , Sangue Fetal/análise , Genótipo , Humanos , Malária/sangue , Polinésia , Talassemia/genéticaRESUMO
A study of genotypes in alpha thalassemia and their corresponding hematological phenotypes has shown that alpha(+) thalassemia is the most frequent type encountered in a Sydney population. Phenotypes of heterozygous alpha(+) thalassemia (alpha alpha/-alpha) in adults or children differ little from normal and so the disorder is difficult to identify. In contrast, Hb Bart's (gamma 4) is a useful marker for alpha alpha/-alpha in cord blood samples. Abnormal phenotypes are present in homozygous alpha(+) thalassemia (-alpha/-alpha), heterozygous alpha(0) thalassemia (alpha alpha/--) and non-deletional alpha thalassemia. Therefore, detection by routine hematological studies should be possible. A less severe phenotype in -alpha/-alpha compared to alpha alpha/-- was found which is interesting since 2 alpha globin genes are lost in both instances.
Assuntos
Mapeamento Cromossômico , DNA/genética , Talassemia/genética , Adulto , Austrália , Criança , Enzimas de Restrição do DNA , Feminino , Genótipo , Hemoglobinometria , Hemoglobinas Anormais/análise , Humanos , Masculino , Fenótipo , Talassemia/diagnósticoRESUMO
Alpha thalassaemia as a cause of hypochromic, microcytic anaemia in pregnancy is described. The problems associated with accurate diagnosis of this condition and prediction of fetal outcome is now made much easier by use of recombinant DNA techniques such as gene mapping. Two Greek Cypriot families with alpha thalassaemia have been studied by DNA mapping. Definitive assessment of alpha thalassaemia genotype in these cases enabled confident genetic counselling.
Assuntos
Complicações Hematológicas na Gravidez/genética , Talassemia/genética , Adulto , Mapeamento Cromossômico , DNA/genética , Feminino , Aconselhamento Genético , Genótipo , Humanos , Masculino , Gravidez , Complicações Hematológicas na Gravidez/diagnóstico , Talassemia/diagnósticoRESUMO
Application of the technique of gene mapping has made possible accurate assessment of the alpha thalassemia defect in cord blood samples obtained in a Sydney teaching hospital. Results showed a 5.2% incidence of the alpha+ thalassemia haplotype in the population being tested. Various hematological parameters such as hemoglobin, mean corpuscular hemoglobin, hemoglobin EPG pattern at pH 8.9 and the percentage of hemoglobin Bart's determined by elution at pH 6.7 were measured to assess which would be the most useful in diagnosis of alpha thalassemia at this time of life. The most consistent test proved to be hemoglobin EPG pattern at pH 8.9, and reasons for this are discussed.